Antibacterial and antibiofilm activities of thiazolidine-2,4-dione and 4-thioxo-thiazolidin-2-one derivatives against multidrug-resistant Staphylococcus aureus clinical isolates.

AIMS: Antimicrobial resistance is one of the highest priorities in global public health with Staphylococcus aureus among the most important microorganisms due to its rapidly evolving antimicrobial resistance. Despite all the efforts of antimicrobial stewardship, research and development of new antimicrobials are still imperative. The thiazolidine ring is considered a privileged structure for the development of new antimicrobials. This study aimed to compare the antibacterial effects of two analogue series of thiazolidine-2,4-dione and 4-thioxo-thiazolidin-2-one against multidrug-resistant Staph. aureus clinical isolates. METHODS AND RESULTS: The derivatives 1a, 2a and 2b exhibited MIC between 1-32 µg ml-1 , with time-to-kill curves showing a bactericidal effect up to 24 h. In the antibiofilm assay, the most active derivatives were able to inhibit about 90% of biofilm formation. The 4-thioxo-thiazolidine-2-one derivatives were more active against planktonic cells, while the thiazolidine-2,4-dione derivatives were able to disrupt about 50% of the preformed biofilm. In the in vivo infection model using Caenorhabditis elegans as a host, the derivatives 1a, 2a and 2b increased nematode survival with a concentration-dependent effect. Exposure of Staph. aureus to the derivatives 2a and 2b induced surface changes and decrease cell size. None of the derivatives was cytotoxic for human peripheral blood mononuclear cells (PBMC) but showed moderate cytotoxicity for L929 fibroblasts. CONCLUSION: The 5-(3,4-dichlorobenzylidene)-4-thioxothiazolidin-2-one (2b) was the most active derivative against Staph. aureus and showed higher selective indices. SIGNIFICANCE AND IMPACT OF THE STUDY: 4-thioxo-thiazolidin-2-one is a promising scaffold for the research and development of new antimicrobial drugs against multidrug-resistant Staph. aureus.

Antimicrobial Peptide Analogs From Scorpions: Modifications and Structure-Activity.

The rapid development of multidrug-resistant pathogens against conventional antibiotics is a global public health problem. The irrational use of antibiotics has promoted therapeutic limitations against different infections, making research of new molecules that can be applied to treat infections necessary. Antimicrobial peptides (AMPs) are a class of promising antibiotic molecules as they present broad action spectrum, potent activity, and do not easily induce resistance. Several AMPs from scorpion venoms have been described as a potential source for the development of new drugs; however, some limitations to their application are also observed. Here, we describe strategies used in several approaches to optimize scorpion AMPs, addressing their primary sequence, biotechnological potential, and characteristics that should be considered when developing an AMP derived from scorpion venoms. In addition, this review may contribute towards improving the understanding of rationally designing new molecules, targeting functional AMPs that may have a therapeutic application.

Insights of antiparasitic activity of sodium diethyldithiocarbamate against different strains of Trypanosoma cruzi.

Chagas disease is caused by Trypanosoma cruzi and affects thousands of people. Drugs currently used in therapy are toxic and have therapeutic limitations. In addition, the genetic diversity of T. cruzi represents an important variable and challenge in treatment. Sodium diethyldithiocarbamate (DETC) is a compound with pharmacological versatility acting as metal chelators and ROS generation. Thus, the objective was to characterize the antiparasitic action of DETC against different strains and forms of T. cruzi and their mechanism. The different strains of T. cruzi were grown in LIT medium. To evaluate the antiparasitic activity of DETC, epimastigote and trypomastigote forms of T. cruzi were used by resazurin reduction methods and by counting. Different response patterns were obtained between the strains and an IC50 of DETC ranging from 9.44 ± 3,181 to 60.49 ± 7.62 µM. Cell cytotoxicity against 3T3 and RAW cell lines and evaluated by MTT, demonstrated that DETC in high concentration (2222.00 µM) presents low toxicity. Yet, DETC causes mitochondrial damage in T. cruzi, as well as disruption in parasite membrane. DETC has antiparasitic activity against different genotypes and forms of T. cruzi, therefore, representing a promising molecule as a drug for the treatment of Chagas disease.

Antifungal and Antibiofilm Activities of B-Type Oligomeric Procyanidins From Commiphora leptophloeos Used Alone or in Combination With Fluconazole Against Candida spp.

Commiphora leptophloeos (Burseraceae) is a medicinal plant native to Brazil which is popularly used for treating oral and vaginal infections. There has been no scientific evidence pointing to its efficacy in the treatment of these infections. Thus, this study sought to investigate the cytotoxic, antifungal, and antibiofilm activity of C. leptophloeos against Candida spp. and to isolate, identify, and quantify the content of B-type oligomeric procyanidins (BDP) in the extract of C. leptophloeos stem bark. The extract and the n-butanol fraction were obtained by maceration and liquid-liquid partition, respectively. Phytochemical analysis performed by HPLC-PDA/ELSD and FIA-ESI-IT-MS/MS allowed the identification and quantification of BDP in the samples. The application of centrifugal partition chromatography helped isolate BDP, which was identified by 1H NMR and MS analyses. Candida spp. reference strains and clinical isolates (including fluconazole-resistant strains) derived from the blood cultures of candidemic patients and the vaginal secretion of patients with vulvovaginal candidiasis were used for evaluating the antifungal and antibiofilm effects. Minimal inhibitory concentration (MIC) and minimal fungicidal concentration (MFC) were determined by the microdilution technique, and biofilm inhibition was evaluated through crystal violet and XTT assays. The combined action of BDP with fluconazole was determined by the checkerboard method. The extract, the n-butanol fraction, and the BDP exhibited antifungal activity with MIC values ranging from 312.5 to 2500 µg/mL and were found to significantly reduce the biofilm formed in all the Candida strains investigated. BDP showed a fungicidal potential against strains of Candida spp. (especially against fluconazole-resistant strains), with MIC and MFC values ranging from 156.2 to 2500 µg/mL. In addition, the combined application of BDP and fluconazole produced synergistic antifungal effects against resistant Candida spp. (FICI = 0.31-1.5). The cytotoxic properties of the samples evaluated in human erythrocytes through hemolytic test did not show hemolytic activity under active concentrations. The findings of the study show that C. leptophloeos has antifungal and antibiofilm potential but does not cause toxicity in human erythrocytes. Finally, BDP, which was isolated for the first time in C. leptophloeos, was found to exhibit antifungal effect against Candida spp. either when applied alone or in combination with fluconazole.

A rheological approach to identify efficient biopolymer producing bacteria.

This study investigates the relationship between collective motion and propulsion of bacterial consortia and their biopolymer production efficiency. Rheological tests were conducted for suspensions of two different methanotrophic bacterial consortia obtained after enrichment of sediment samples from mangrove sites in Brazil. We considered the linear viscoelasticity region and analyzed the values of storage and loss moduli as functions of days of cultivation, for different values of the volume fraction. The suspensions' rheological behaviors reflected the bacterial growth stage. We found that the formation of structures over time in some types of consortia can hinder the movement of bacteria in the search for nutrients. The change in complex viscosity of the two consortia followed a different and rich behavior that appears to be closely related to their capacity to capture methane. Our analysis showed a possible correlation between collective motion, viscosity reduction, and biopolymer production. The pieces of evidence from this study suggest that the efficiency of bacterial motion is directly related to biopolymer production, and this could facilitate the process of identifying the best consortium of biopolymer producing bacteria.

Potent and Broad-Spectrum Antimicrobial Activity of Analogs from the Scorpion Peptide Stigmurin.

Scorpion venom constitutes a rich source of biologically active compounds with high potential for therapeutic and biotechnological applications that can be used as prototypes for the design of new drugs. The aim of this study was to characterize the structural conformation, evaluate the antimicrobial activity, and gain insight into the possible action mechanism underlying it, for two new analog peptides of the scorpion peptide Stigmurin, named StigA25 and StigA31. The amino acid substitutions in the native sequence for lysine residues resulted in peptides with higher positive net charge and hydrophobicity, with an increase in the theoretical helical content. StigA25 and StigA31 showed the capacity to modify their structural conformation according to the environment, and were stable to pH and temperature variation-results similar to the native peptide. Both analog peptides demonstrated broad-spectrum antimicrobial activity in vitro, showing an effect superior to that of the native peptide, being non-hemolytic at the biologically active concentrations. Therefore, this study demonstrates the therapeutic potential of the analog peptides from Stigmurin and the promising approach of rational drug design based on scorpion venom peptide to obtain new anti-infective agents.

Potent and broad-spectrum antimicrobial activity of analogs from the scorpion peptide Stigmurin

Scorpion venom constitutes a rich source of biologically active compounds with high potential for therapeutic and biotechnological applications that can be used as prototypes for the design of new drugs. The aim of this study was to characterize the structural conformation, evaluate the antimicrobial activity, and gain insight into the possible action mechanism underlying it, for two new analog peptides of the scorpion peptide Stigmurin, named StigA25 and StigA31. The amino acid substitutions in the native sequence for lysine residues resulted in peptides with higher positive net charge and hydrophobicity, with an increase in the theoretical helical content. StigA25 and StigA31 showed the capacity to modify their structural conformation according to the environment, and were stable to pH and temperature variationresults similar to the native peptide. Both analog peptides demonstrated broad-spectrum antimicrobial activity in vitro, showing an effect superior to that of the native peptide, being non-hemolytic at the biologically active concentrations. Therefore, this study demonstrates the therapeutic potential of the analog peptides from Stigmurin and the promising approach of rational drug design based on scorpion venom peptide to obtain new anti-infective agents.

Multivariate Relationships among Morphology, Fitness and Motor Coordination in Prepubertal Girls.

Motor coordination and physical fitness are multidimensional concepts which cannot be reduced to a single variable. This study evaluated multivariate relationships among morphology, physical fitness and motor coordination in 74 pre-pubertal girls 8.0-8.9 years of age. Data included body dimensions, eight fitness items and four motor coordination tasks (KTK battery). Maturity status was estimated as percentage of predicted mature stature attained at the time of observation. Canonical correlation analysis was used to examine the relationships between multivariate domains. Significant pairs of linear functions between indicators of morphology and fitness (rc = 0.778, Wilks' Lambda = 0.175), and between fitness and motor coordination (rc = 0.765, Wilks' Lambda = 0.289) were identified. Girls who were lighter and had a lower waist-to-stature ratio and % fat mass attained better scores in the endurance run, sit-ups and standing long jump tests, but poorer performances in hand grip strength and 2-kg ball throw. Better fitness test scores were also associated with better motor coordination scores. Relationships between body size and estimated fatness with motor fitness suggested an inverse relationship that was particularly evident in performance items that required the displacement of the body through space, while motor coordination was more closely related with fitness than with somatic variables.

Situação dos extintores de incêndio em estabelecimentos comerciais do município de Vitória da Conquista, Bahia / Contidition of fire extinghishers in some commercial buildings in the municipality of Vitória da Conquista, Bahia / Situación de los extintores de incendio de establecimientos comerciales del municipio de Vitória da Conquista, Bahia

Fogo é necessário para a humanidade, entretanto, muitas vezes, fica fora de controle e passa a ser um agente causador de incêndios, destruição do meio ambiente e mortes, seja na área urbana ou na área rural. Os extintores de incêndio são aparelhos destinados a combater o princípio de incêndio. O objetivo deste estudo foi verificar, nos estabelecimentos comerciais de Vitória da Conquista, Bahia, Brasil, se os extintores portáteis de combate a incêndio estão instalados de acordo com as normas vigentes de proteção, enfatizando a instalação, a visibilidade e se estão desobstruídos. Trata-se de um estudo exploratório descritivo, com abordagem qualitativa, executado mediante a técnica de observação, que envolveu 30 estabelecimentos comerciais. Utilizou-se a técnica de observação descritiva, por ser uma importante fonte de coleta de informações sobre o objeto de análise proposto ­ os extintores portáteis de incêndio. Os resultados mostraram que todos os estabelecimentos comerciais observados tinham extintores. Todos eles (100%) estavam obstruídos e 80% sem sinalização. Concluiu-se que os extintores de incêndio dos 30 estabelecimentos comerciais de Vitória da Conquista encontravam-se em desacordo com as normas vigentes, no tocante à instalação, localização, sinalização, visibilidade e desobstrução.

Fire is a necessity to mankind. However, fire is also a threat because when out of control it causes deaths, destructions and damages to rural and urban environments. Fire extinguishers are equipment used to fight the beginning of fire. The objective of this study was to verify whether the portabel fire extinguishers installed in the commercial buildings of Vitória da Conquista, Bahia, Brasil are in compliance to regulatory norms with emphasis on installation, visibility and unblock aspects. It´s a descriptive exploratory study with a qualitative approach, executed through the technique of observation, comprising 30 commercial buildings. It was used the technique of descriptive observation because this is an important source of information collection about the subject under analysis - portable fire extinguishers. The results shows that all observed commercial buildings have extinguishers installed. All of them (100%) were obstructed and 80% have no indication of safety sign. It was possible to conclude that the fire extinguishers of the 30 commercial establishments of Vitória da Conquista were not compliance to regulatory norms regarding installation, localization, signalization, visibility and unblock.

Fuego es necesario para la humanidad, todavía, cuando fuera de control, provoca incendios, destrucción del medio ambiente y muertes tanto en áreas urbanas como rurales. Los extintores son aparatos que se destinan al combate del principio de incendio. El objetivo de este trabajo fue averiguar en los establecimientos comerciales de Vitória da Conquista, Bahia, Brasil, si los extintores portátiles de combate a incendio están instalados en consonancia con las normas reglamentares, con énfasis en aspectos relacionados con la instalación, con la visibilidad y con la desobstrucción. Tratase de un estudio exploratorio descriptivo, con abordaje cualitativo, ejecutado mediante la técnica de observación, que envolvió 30 estabelecimientos comerciales. Fue utilizada la técnica de observación descriptiva por ser una importante fuente de recopilación de informaciones sobre el objeto de análisis propuesto ­ los extintores portátiles de incendio. Los resultados muestran que todos los estabelecimientos comerciales observados tenían extintores. Pero, el 100% de estos estaban obstruidos y el 80% no estaban señalizados. Concluyóse que la los extintores de incendio de los 30 establecimientos comerciales de Vitória da Conquista estaban en desacuerdo con las normas reglamentares en lo que se refiere a la instalación, localización, señalización, visibilidad y desobstrucción.

Waist circumference as a mediator of biological maturation effect on the motor coordination in children / Perímetro de cintura como mediador da influência da maturação biológica no desempenho de coordenação motora em crianças

Abstract Objective: The present study aimed to: 1) examine the association of biological maturation effect on performance at a motor coordination battery and 2) to assess whether the association between biological maturation and scores obtained in motor coordination tests is mediated by some anthropometric measurement. Methods: The convenience sample consisted of 73 male children aged 8 years old. Anthropometric data considered the height, body mass, sitting height, waist circumference, body mass index, fat mass and fat-free mass estimates. Biological maturation was assessed by the percentage of the predicted mature stature. Motor coordination was tested by the Körperkoordinationstest für Kinder. A partial correlation between anthropometric measurements, z-score of maturation and the motor coordination tests were performed, controlling for chronological age. Finally, causal mediation analysis was performed. Results: Height, body mass, waist circumference and fat mass showed a slight to moderate inverse correlation with motor coordination. Biological maturation was significantly associated with the balance test with backward walking (r=-0.34). Total mediation of the waist circumference was identified in the association between biological maturation and balance test with backward walking (77%). Conclusions: We identified an association between biological maturation and KTK test performance in male children and also verified that there is mediation of waist circumference. It is recommended that studies be carried out with female individuals and at other age ranges.

Resumo Objetivo: O presente estudo teve como objetivos: 1) analisar a associação do estado maturacional com o desempenho nas provas de coordenação motora em crianças e 2) examinar se a relação entre o estado maturacional e o desempenho no KTK é mediada por alguma medida antropométrica. Métodos: A amostra de conveniência foi composta por 73 crianças do sexo masculino com 8 anos. A antropometria considerou a estatura, massa corporal, altura sentado, o perímetro de cintura, índice de massa corporal, as estimativas de massa gorda e massa livre de gordura. A maturação biológica foi avaliada pelo percentual da estatura matura predita. A coordenação motora foi testada pela bateria Körperkoordinationstest für Kinder. Foi feita a correlação parcial entre as medidas antropométricas, z-escore da maturação e as provas de coordenação motora, com controle para idade cronológica. Por último, a análise de mediação causal foi feita. Resultados: Estatura, massa corporal, perímetro de cintura e massa gorda apresentaram correlação inversa de magnitude pequena a moderada com as provas de coordenação motora. A maturação biológica associou-se significativamente à prova de equilíbrio em marcha à retaguarda (r=-0,34). Foi identificada mediação total do perímetro de cintura na relação do estado maturacional com o equilíbrio em marcha à retaguarda (77%). Conclusões: Foi possível identificar a associação entre o estado físico maturacional e o desempenho em uma prova de bateria de coordenação motora em crianças do sexo masculino e, ainda, afirmar que há mediação do perímetro de cintura. Recomenda-se que estudos sejam feitos com indivíduos de outras idades e do sexo feminino.

Independent and Combined Effects of Sex and Biological Maturation on Motor Coordination and Performance in Prepubertal Children.

Sex differences and maturation-associated variation in fitness and motor coordination were examined in children aged 8-9 years (n = 128, 67 girls). Assessments included stature and body mass, two-component body composition, percentage of predicted adult stature (as an index of biological maturation), and motor performance and coordination (Körperkoordinationstest für Kinder). Compared to girls, boys were less advanced in maturation status, possessed larger fat mass, demonstrated superior performances in six tests of fitness, and obtained one superior score on the Körperkoordinationstest für Kinder. After controlling for somatic maturation, sex differences persisted in the two multivariate domains: motor performance and motor coordination.

Waist circumference as a mediator of biological maturation effect on the motor coordination in children. / Perímetro de cintura como mediador da influência da maturação biológica no desempenho de coordenação motora em crianças.

OBJECTIVE: The present study aimed to: 1) examine the association of biological maturation effect on children's performance at a motor coordination battery and 2) to assess whether the association between biological maturation and scores obtained in motor coordination tests is mediated by some anthropometric measurement. METHODS: The convenience sample consisted of 73 male children aged 8 years old. Anthropometric data considered the height, body mass, sitting height, waist circumference, body mass index, fat mass and fat-free mass estimates. Biological maturation was assessed by the percentage of the predicted mature stature. Motor coordination was tested by the Körperkoordinationstest für Kinder. A partial correlation between anthropometric measurements, z-score of maturation and the motor coordination tests were performed, controlling for chronological age. Finally, causal mediation analysis was performed. RESULTS: Height, body mass, waist circumference and fat mass showed a slight to moderate inverse correlation with motor coordination. Biological maturation was significantly associated with the balance test with backward walking (r=-0.34). Total mediation of the waist circumference was identified in the association between biological maturation and balance test with backward walking (77%). CONCLUSIONS: We identified an association between biological maturation and KTK test performance in male children and also verified that there is mediation of waist circumference. It is recommended that studies be carried out with female individuals and at other age ranges.

Perímetro abdominal: evidências para a predição da gordura corporal subcutânea em meninos escolares / Abdominal girth: evidence for the prediction of subcutaneous body fat in student boys

Introdução: O diagnóstico de sobrepeso e obesidade pode ser realizado pela antropometria, por facilidade de execução e baixo custo. Considerando a preocupação com a característica de distribuição de gordura, novas estratégias poderiam ser desenvolvidas para a avaliação da composição corporal partindo de medidas antropométricas. Objetivos: Verificar a correlação do Perímetro Abdominal (PAB) e Perímetro da Cintura (PC) em separado, com o somatório de duas dobras cutâneas (DC), triciptal e subescapular; e incluir o perímetro com os maiores valores de correlação em uma equação de regressão para estimativa do somatório de DC. Métodos: Amostra composta por 1.729 meninos (9 e 14 anos), a avaliação da morfologia corporal foi realizada por medidas antropométricas simples e compostas. Foi utilizada uma correlação de Spearman para determinar a associação entre os PAB e PC com as DC. Foi feita uma análise de regressão linear múltipla com o PAB e idade para estimar o somatório de DC. Resultados: A seguinte equação foi gerada: Somatório de DC = 1,16397 (PAB) ­ 1,414922 (Idade) ­ 36,33021 (R=0,83). O valor da área sob a curva ROC (AUC) foi de 83% para identificar corretamente indivíduos abaixo ou acima do percentil 85 do somatório de DC. Conclusões: O PAB em conjunto com a idade, se torna um bom preditor da gordura corporal, caracterizada como o somatório de DC, em crianças e adolescentes do sexo masculino.

Introduction: The diagnosis of overweight and obesity can be accomplished by anthropometry, for ease of implementation and low cost. Considering the concern for the distribution of fat, new strategies could be developed for the diagnosis of body composition from anthropometric measurements. Objectives: To investigate the association of the abdominal girth (AG) and waist girth (WG) separately, with the sum of two skinfolds (SF), triceps and subscapular; and include the girth with higher correlation levels in a regression equation to estimate the SF sum. Methods: A sample of 1,729 boys (9 and 14), the evaluation of body composition was composed by simple and compound anthropometric measurements. The Spearman correlation was used to determine the association between AG and WG with the sum of SF. A multiple linear regression was applied including AG and age to estimate the sum of SF. Results: The following equation was generated: Sum of SF = 1.16397 (AG) - 1.414922 (age) - 36.33021 (R = 0.83). The area under the ROC curve (AUC) was 83% for correctly identifying individuals below or above the 85th percentile of the SF sum. Conclusions: AG, together with age, becomes a good predictor of body fat, characterized as the sum of two SF in children and adolescent males.